J 2017

Co-delivery of VP-16 and Bcl-2-targeted antisense on PEG-grafted oMWCNTs for synergistic in vitro anti-cancer effects in non-small and small cell lung cancer

HEGER, Zbynek, Hana POLANSKÁ, Sona KRIZKOVA, Jan BALVAN, Martina RAUDENSKÁ et. al.

Basic information

Original name

Co-delivery of VP-16 and Bcl-2-targeted antisense on PEG-grafted oMWCNTs for synergistic in vitro anti-cancer effects in non-small and small cell lung cancer

Authors

HEGER, Zbynek (203 Czech Republic), Hana POLANSKÁ (203 Czech Republic, belonging to the institution), Sona KRIZKOVA (203 Czech Republic), Jan BALVAN (203 Czech Republic, belonging to the institution), Martina RAUDENSKÁ (203 Czech Republic, belonging to the institution), Simona DOSTALOVA (203 Czech Republic), Amitava MOULICK (203 Czech Republic), Michal MASAŘÍK (203 Czech Republic, guarantor, belonging to the institution) and Vojtech ADAM (203 Czech Republic)

Edition

Colloids and Surfaces B: Biointerfaces, Amsterdam, Elsevier, 2017, 0927-7765

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30105 Physiology

Country of publisher

Netherlands

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 3.997

RIV identification code

RIV/00216224:14110/17:00095967

Organization unit

Faculty of Medicine

UT WoS

000393726900016

Keywords in English

Drug delivery; Etoposide; In vitro release; Multi-walled carbon nanotubes; Nanomedicine

Tags

Tags

International impact, Reviewed
Změněno: 15/3/2018 16:24, Soňa Böhmová

Abstract

V originále

Present study describes the preparation of a polyethylene glycol-grafted oxidized multi-walled carbon nanotubes (oMWCNTs-PEG) hybrid nanosystem as a carrier of etoposide (VP-16) and Bcl-2 phosphorothioate antisense deoxyoligonucleotides (Aso) to achieve a superior cytostastic efficacy in non-small and small cell lung cancer in vitro. We have demonstrated that the adsorption of hydrophobic VP-16 and Bcl-2 Aso results in a stable nanotransporter exhibiting good dispersion with excellent release profiles (both, in pH 7.4 and 4.8) and negligible hemolytic activity (up to 6.5%). The evaluation of cytotoxicity was carried out in in vitro using small cell (SCLC; DMS53) and non-small cell lung cancer (NSCLC; NCIH2135) cell lines. It was found that Bcl-2 interference significantly increased the anti-cancer efficiency of VP-16 in the chemoresistant NSCLC cells. This was further supported using a flow-cytometry (Annexin V/propidium iodide assay), which revealed a significant increase in apoptotic cells in both the cell lines after the co-administration of VP-16 and Bcl-2 Aso using oMWCNTs-PEG hybrid, and fluorescence microscopy, which showed an increase in reactive oxygen species identified after Bcl-2 knock-down. Overall, oMWCNTs-PEG provided an exceptional biocompatible vehicle enabling the internalization of negatively charged nucleic acids and pH-sensitive release of cargoes in a hypoxic environment of the most of solid tumors. Moreover, Aso specifically binding to the first six codons of the Bcl-2 mRNA gave a satisfactorily decrease in Bcl-2 translation and an increase in NCIH2135 chemosensitivity towards VP-16.